Association of periodontitis and oral microbiomes with Alzheimer's disease: A narrative systematic review.

Background/purpose: Alzheimer's disease (AD) is a neurodegenerative disorder and the most common form of dementia. The etiology for AD includes age, genetic susceptibility, neuropathology, and infection. Periodontitis is an infectious and inflammatory disease which mainly causes alveolar bone destruction and tooth loss. The evidence of a link between AD and periodontitis remains controversial. Thus far, studies reviewing the association between AD and periodontal disease have been insufficient from the viewpoint of the oral microbiome. The aim of this review was to focus on studies that have explored the relationship between the oral microbiome and AD development by using the next-generation sequencing technique. Materials and methods: A comprehensive electronic search of MEDLINE via PubMed, EMBASE, Scopus, and Google Scholar was conducted. The keywords included dementia, Alzheimer's disease, cognitive impairment, periodontitis, periodontal disease, and oral microbiome. Results: This review included 26 articles based on the eligibility criteria. Epidemiologic researches and post-mortem studies showed that the presence of periodontitis is associated with cognitive decline, suggesting a possible role of periodontal pathogens in the pathogenesis of AD. The reported microbiome was inconsistent with those in gene sequencing studies. Nevertheless, Gram-negative species may be possible candidates. Conclusion: This review suggests that periodontal infection is associated with AD. The contributing microbiome remains unconfirmed, possibly because of different microbiome sampling sites or methods. Additional large-scale studies with periodontal intervention and longitudinal follow-up are warranted to clarify the relationship between periodontal disease and AD.

Platelet-Derived Biomaterials Inhibit Nicotine-Induced Intervertebral Disc Degeneration Through Regulating IGF-1/AKT/IRS-1 Signaling Axis.

Apart from aging process, adult intervertebral disc (IVD) undergoes various degenerative processes. However, the nicotine has not been well identified as a contributing etiology. According to a few studies, nicotine ingestion through smoking, air or clothing may significantly accumulate in active as well as passive smokers. Since nicotine has been demonstrated to adversely impact various physiological processes, such as sympathetic nervous system, leading to impaired vasculature and cellular apoptosis, we aimed to investigate whether nicotine could induce IVD degeneration. In particular, we evaluated dose-dependent impact of nicotine in vitro to simulate its chronic accumulation, which was later treated by platelet-derived biomaterials (PDB). Further, during in vivo studies, mice were subcutaneously administered with nicotine to examine IVD-associated pathologic changes. The results revealed that nicotine could significantly reduce chondrocytes and chondrogenic indicators (Sox, Col II and aggrecan). Mice with nicotine treatment also exhibited malformed IVD structure with decreased Col II as well as proteoglycans, which was significantly increased after PDB administration for 4 weeks. Mechanistically, PDB significantly restored the levels of IGF-1 signaling proteins, particularly pIGF-1 R, pAKT, and IRS-1, modulating ECM synthesis by chondrocytes. Conclusively, the PDB impart reparative and tissue regenerative processes by inhibiting nicotine-initiated IVD degeneration, through regulating IGF-1/AKT/IRS-1 signaling axis.

Modulating redox homeostasis and cellular reprogramming through inhibited methylenetetrahydrofolate dehydrogenase 2 enzymatic activities in lung cancer.

Recent reports have indicated the role of highly expressed methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) enzyme in cancers, showing poor survival; however, detailed mechanistic insight of metabolic functions of MTHFD2 have not been well-defined. Therefore, we aimed to examine the metabolic functions and cellular reprograming potential of MTHFD2 in lung cancer (LCa). In this study, we initially confirmed the expression levels of MTHFD2 in LCa not only in tissue and OncomineTM database, but also at molecular levels. Further, we reprogrammed metabolic activities in these cells through MTHFD2 gene knockdown via lentiviral transduction, and assessed their viability, transformation and self-renewal ability. In vivo tumorigenicity was also evaluated in NOD/SCID mice. Results showed that MTHFD2 was highly expressed in stage-dependent LCa tissues as well in cell lines, A549, H1299 and H441. Cellular viability, transformation and self-renewal abilities were significantly inhibited in MTHFD2-knockdown LCa cell lines. These cells also showed suppressed tumor-initiating ability and reduced tumor size compared to vector controls. Under low oxygen tension, MTHFD2-knockdown groups showed no significant increase in sphere formation, and hence the stemness. Conclusively, the suppressed levels of MTHFD2 is essential for cellular metabolic reprogramming leading to inhibited LCa growth and tumor aggressiveness.